What the FDA labels say about taking them together
Hydrocodone and midazolam
Midazolam's FDA label (Nayzilam) of January 19, 2023 names hydrocodone in its drug interactions section; hydrocodone's label does not name midazolam itself but warns about its class (Benzodiazepines). The midazolam label: “The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. …”
Check it at the source: the hydrocodone FDA label on DailyMed (effective May 29, 2026); the midazolam FDA label on DailyMed (effective January 1, 2024, Fresenius Kabi USA, LLC).
What does the hydrocodone label say about midazolam?
Hydrocodone's label does not name midazolam itself; it warns about its class (Benzodiazepines):
Hydrocodone label, boxed warningInstruct patients to swallow HYSINGLA ER whole to avoid exposure to a potentially fatal dose of hydrocodone. ( 5.2 ) Accidental ingestion of HYSINGLA ER, especially by children, can result in fatal overdose of hydrocodone. ( 5.2 ) Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Hydrocodone label, boxed warningRisks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Source: FDA drug label (Hysingla ER), Knoa Pharma LLC, effective May 29, 2026 (SPL set b7d23ac2-e776-9f62-3290-c64c2d6eb353), via openFDA; the full label on DailyMed
What does the midazolam label say about hydrocodone?
Nayzilam label (UCB, Inc., January 19, 2023), drug interactions7.2 Opioids Clinical Impact: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors. … Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required [see ]. Examples: Morphine, hydrocodone, oxymorphone, codeine, fentanyl
Source: FDA drug label (Nayzilam, NDA211321), UCB, Inc., effective January 19, 2023 (SPL set 2b29422e-54d5-4a49-8522-e9cf752368c3), via openFDA
Source: FDA drug label (Midazolam), Fresenius Kabi USA, LLC, effective January 1, 2024 (SPL set 1cc9ba6e-fa1b-405e-9de8-720c567b2a73), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Hydrocodone | Midazolam | |
|---|---|---|
| Labeled for | Pain | n/a |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $7.95 per capsule 15 mg capsule | $0.233 per mL 2 mg/2 mL vial |
| Shortage now | No current entry | In shortage |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once